Inflammatory Response after Immediate versus Delayed Ex-Vivo Lung Perfusion in a Porcine Cardiac Arrest Donation Model

Abstract

Ex Vivo Lung Perfusion (EVLP) is a promising tool for evaluation and reconditioning in marginal donor lungs. However, the optimal protocol is discussed controversially. It is our hypothesis that different EVLP protocols and different perfusion solutions result in different cytokine patterns during EVLP. Following cardiac arrest and 30 min of no-touch warm ischemia, pig lungs were harvested, flushed and stored in cold preservation solutions. Different groups were processed as immediate long EVLP (I-EVLP, 12 h), delayed short EVLP (4 h) after 9 hours of cold storage (D-EVLP). Lungs were perfused with different acellular solutions: Steen solution or modified HTK solution containing either dextran(CD) or dextran and albumin (CDA). Pulmonary gas exchange, biochemical and structural parameters were recorded hourly. Cytokine / chemokine levels were analyzed in perfusates at baseline and after 1 and 4 h of EVLP. ∆ pO2 (pulmonary venous - pulmonary arterialpO2) was higher in D-EVLP group, especially at h 1: I-EVLP: 259 ± 132, D-EVLP: 291 ± 96 and h 2: I-EVLP: 228 ± 125, D-EVLP: 252 ± 116 (n.s.). Compared to D-EVLP, lungs that underwent EVLP with CD and CDA showed significantly higher oxygen capacity (∆ pO2 CD: 402.79 +30.33 mmHg, CDA: 414.86 + 9.77 mmHg). Within 4 h ELVP, concentrations of IFN-γ, TNF-a, IL-1α/β, IL-10, CXCL8 (IL-8) and IL-18 increased significantly (all p<0.05) in the four groups. Of note, no significant differences could be detected between I- vs. D-EVLP lungs and CD vs. CDA solutions. In a non-heart beating porcine lung donor model with relevant ischemic tissue damage, lungs were perfused with normothermic EVLP. Even after 9 hours cold static preservation (CSP) and 4 hours EVLP lung, function is comparable to direct EVLP. The modified HTK solution with dextran and dextran/ albumin had significantly better oxygenation. Cytokines and chemokines including the cell death marker IL-18 increase during 4 h of EVLP but a delay before EVLP may not dramatically worsen the inflammatory response.